The interferons represent a group of biologically active glycoproteins with proven anti-viral and anti-neoplastic properties. Several subtypes of interferon have been defined based upon differences in antigenic and biological properties. The interferon subtypes are alpha interferon, beta interferon and gamma interferon.
Advances in biotechnical research in the past 10 years have resulted in the production of highly purified recombinant DNA interferons.
Clinical studies have shown that when used as a single agent, the interferons have antitumor activity in e.g. renal cell carcinoma, melanoma, indolent forms of non-Hodgkin's lymphoma, Kaposi's sarcoma and hairy cell leukemia. Other tumors including ovarian carcinoma and glioblastoma multiforme appeared to be less responsive to interferon. All subtypes of interferon are not active against all the listed tumors.
Radiation therapy is a mainstay in modern cancer treatment with proven efficacy in many human tumors. There is, however, always a need for continued improvement in effectiveness of such treatment. Among the attempts to improve the efficacy of radiation treatment are efforts to develop radiation sensitizers or potentiators which enable the radiation to cause increased tumor destruction. Despite numerous laboratory and clinical studies, no single agent has, to date, emerged as the optimal radiation sensitizer.
There have been a small number of studies in the laboratory involving interferon and radiation therapy, however, the results were inconclusive.
Dritschilo et al., Am. J. Clinic. Onc. 5 79 (1982) studied the effect on IFN on the radiation response of mouse 3T3 cells in tissue culture. A species specific enhancement of radiation killing of 3T3 cells irradiated in the presence of mouse L-cell interferon was observed as a reduction in the shoulder portion of the cell survival curve. Split-dose experiments designed to test for changes in sub-lethal radiation injury repair failed to demonstrate an inhibitory interferon effect. Dritschilo et al., postulate that interferon potentiates radiation injury possibly by inhibiting the ability of the cultured cells to accumulate sub-lethal radiation injury.
Namba et al., Cancer 54, 2262 (1984) confirmed the Dritschilo et al., observations in a study of the combined use of interferon and radiation therapy using HeLa cells.
Gould et al., J. Interferon Research 4 123 (1984) observed in vitro radiosensitization of human bronchogenic carcinoma with beta interferon but not with alpha interferon. Gould et al. noted that the degree of radiosensitization of the various interferons paralleled their anti-proliferative effects when used alone on the bronchogenic cell lines. Nevertheless, Gould et al. concluded that the ant-neoplastic effects of the combined use of interferon and radiation were supra-additive indicating radiosensitization.
Nederman et al., Acta Radiologica Oncology, 21, 231 (1982) observed enhanced growth retardation in human glioma cell cultures following combined therapy in comparison to interferon and radiotherapy used alone. Nederman et al. attributes their results to the additive antineoplastic effect of the radiation and interferon but could not confirm radiosensitization.
Combined radiation and interferon studies have not been reported in animal model systems, primarily because of the species specificity of interferon; Lvovsky et al., Int. J. Rad. Onc. Bio. Phys. 11, 1721 (1985) observed enhanced tumor control using the interferon inducer, poly ICLC and radiation, and radiation in the mouse Lewis lung tumor model. A delay in tumor regrowth and a prolonged duration of survival were observed in the inducer plus radiation animals as compared to either inducer or radiation alone.
Mahaley et al., J. Bio. Res. Modifiers 3 19 (1984) reported a phase I study of the combined use of interferon and radiation therapy in nine patients with anaplastic glioma following subtotal resection. Patient survival was comparable to that for a matched group with combined BCNU and radiation therapy. Other reports show unexpected increases in toxicity when combined therapy is used.
Real et al., J. Bio. Resp. Modifiers, 4,141 (1985) reported severe oral cavity mucositis in two patients with Daposi's sarcoma requiring cessation of radiotherapy.
Mattson et al., J. Biol. Resp. Modifiers 4, 8-17 (1985) reported that the concomitant use of interferon and radiotherapy has been associated with an increased incidence of radiation pneumonitis in patients with small cell carcinoma.